**6. Trial on effectiveness of dapagliflozin in uncontrolled T2D using insulin pumps**

Gliflozins are inhibitors of sodium glucose co-transporter 2 (SGLT2) in proximal part of renal tubules. Their influence results in lowering of the renal thresholds for glucose and lowering of hyperglycaemia (due to urine excretion of about 70 g glucose per 24 h). Impact of gliflozins (dapagliflozin [89–91], empagliflozin [92] canagliflozin [93–95] and ertugliflozin) on metabolic control and cardiovascular and renal outcomes in T2D was demonstrated in trials EMPAREG, EMPEROR, CANVAS, CREDENCE, DECLARE HF, DECLARE Timi 58 and VERTIS. Benefits were observed in simultaneous therapy with insulin/incretin and gliflozin. [96]

Our pilot prospective trial (2015–2017) [97] aimed to the assessment of effectiveness of dapagliflozin added to people with T2D treated by CSII and metformin (M). A group of 13 T2D on CSII, without serious complications, aged 44.6–70.4 y, diabetes duration 5–26 y, BMI 24.9–57.6 kg/m2, were monitored at 4 visits (before

**21**

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020*

CSII, on CSII + M, on CSII + M shortly before dapagliflozin and finaly on CSII + M

*A group of T2D (N = 13) treated with 3 consequent regimens: 1. MDI + M, 2. CSII+M, 3. CSII+M + DG. Evolution of relative values of INS/d, HbA1c, MPG, BM. Upper border of the reference range of respective* 

No side effects appeared. So, dapagliflozin may be considered as a rational

This chapter summarizes the authors' experience along with outcomes of respected randomized control trials and real world evidence studies. It became clear that the pathophysiologic approach comprising insulin, incretins and gliflozins has created a reliable base to effective treatment of type 2 diabetes. Reduced morbidity and mortality along with other breaking reports [98–101] are offerring some great

On the other hand, in everyday practice, hidden clinical inertia, resulting from outdated treatment approach, customs, imbalance between powerty and affluency,

R.C. was in charge of the selection of cited references and figures and manuscript design, data analysis and critical text review. R.K. and L.H. supervised the

CSII appeared to enable reduction of total daily insulin dose with no consequent change of HbA1c and glycaemia. Adding dapagliflozin to CSII resulted in significant reduction of HbA1c. (**Figure 26**) Even though the change in BM was not significant, Spearman analysis revealed correlations between the change of daily insulin dose

*DOI: http://dx.doi.org/10.5772/intechopen.96237*

after 2.5–11.0 months with dapagliflozin.

*parameter was defined as 100% of its value (2015–2017) [97].*

and change of BM at visit 3 and 4 vs. visit 1.

should be considered as a dangerous rival. So, which direction do we take from here?

**7. Conclusions**

**Figure 26.**

perspectives.

**Acknowledgements**

therapeutic addition to CSII + M treated people with T2D.

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020 DOI: http://dx.doi.org/10.5772/intechopen.96237*

#### **Figure 26.**

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

We deemed IDegLira could be an option for T2D suffering from impaired cognitive functions. We described this condition as "cast away syndrome".

38 mmol/mol (reference range 20–42 mmol/mol) (**Figures 23–25**).

**6. Trial on effectiveness of dapagliflozin in uncontrolled T2D using** 

part of renal tubules. Their influence results in lowering of the renal thresholds for glucose and lowering of hyperglycaemia (due to urine excretion of about 70 g glucose per 24 h). Impact of gliflozins (dapagliflozin [89–91], empagliflozin [92] canagliflozin [93–95] and ertugliflozin) on metabolic control and cardiovascular and renal outcomes in T2D was demonstrated in trials EMPAREG, EMPEROR, CANVAS, CREDENCE, DECLARE HF, DECLARE Timi 58 and VERTIS. Benefits were observed in simultaneous therapy with insulin/incretin and gliflozin. [96] Our pilot prospective trial (2015–2017) [97] aimed to the assessment of effectiveness of dapagliflozin added to people with T2D treated by CSII and metformin (M). A group of 13 T2D on CSII, without serious complications, aged 44.6–70.4 y, diabetes duration 5–26 y, BMI 24.9–57.6 kg/m2, were monitored at 4 visits (before

Gliflozins are inhibitors of sodium glucose co-transporter 2 (SGLT2) in proximal

Our case report (1995–2020) [88] pays attention to IDegLira in a 77-year-old woman with T2D. Her diabetes was treated for 33 years (since 1985) including the last seven- year period of effective insulin pump therapy, finally combined with dapagliflozin. Recently, signs of cognitive deterioration ("cast away syndrome") appeared and the patient was unable to operate her insulin pump. Adding IDegLira to previous metformin and dapagliflozin therapy alongside with support of educated family lead to improvement of patient's condition. The final in-patient period (30. 4. - 1. 7. 2020]) with IDegLira 40 IU/d (no CSII, no metformin, no gliflozin) and specialized diabetes care of nursing staff resulted in reduction of HbA1c to

*Lady, age 77 y, T2D since 1985, cast away syndrome. Overview of all parameters (HbA1c, BM, insulin/day, MPG) in the course of different therapeutic regimens (MDI-CSII-CSII with iSGLT2-IDegLira only) (1996–2020) [88].*

**20**

**insulin pumps**

**Figure 25.**

*A group of T2D (N = 13) treated with 3 consequent regimens: 1. MDI + M, 2. CSII+M, 3. CSII+M + DG. Evolution of relative values of INS/d, HbA1c, MPG, BM. Upper border of the reference range of respective parameter was defined as 100% of its value (2015–2017) [97].*

CSII, on CSII + M, on CSII + M shortly before dapagliflozin and finaly on CSII + M after 2.5–11.0 months with dapagliflozin.

CSII appeared to enable reduction of total daily insulin dose with no consequent change of HbA1c and glycaemia. Adding dapagliflozin to CSII resulted in significant reduction of HbA1c. (**Figure 26**) Even though the change in BM was not significant, Spearman analysis revealed correlations between the change of daily insulin dose and change of BM at visit 3 and 4 vs. visit 1.

No side effects appeared. So, dapagliflozin may be considered as a rational therapeutic addition to CSII + M treated people with T2D.

### **7. Conclusions**

This chapter summarizes the authors' experience along with outcomes of respected randomized control trials and real world evidence studies. It became clear that the pathophysiologic approach comprising insulin, incretins and gliflozins has created a reliable base to effective treatment of type 2 diabetes. Reduced morbidity and mortality along with other breaking reports [98–101] are offerring some great perspectives.

On the other hand, in everyday practice, hidden clinical inertia, resulting from outdated treatment approach, customs, imbalance between powerty and affluency, should be considered as a dangerous rival.

So, which direction do we take from here?

#### **Acknowledgements**

R.C. was in charge of the selection of cited references and figures and manuscript design, data analysis and critical text review. R.K. and L.H. supervised the

#### *Type 2 Diabetes - From Pathophysiology to Cyber Systems*

performance of therapeutic protocols including HbA1c and 10-point glycaemic profiles, H.Z. was responsible for medical reports, files and IT operations, B.D. took care of laboratory investigations. There is no conflict of interests.

Special thanks to Stanislava Dudová, Emilia Ďurajková, Lenka Kratochvílová, Michaela Nádvorniková, Jana Polcerová, Svatava Tancosová, Jana Ferancová, Pavel Kolčava, Eva Malá, Dana Masnikosová, Hana Peniaková, Jiří Podivínský, Jana Svobodová, Rastislav Šramko and their teams for outstanding neverending support.

Final acknowledgement belongs to specialists, nursing and other staff, students of Palacky University Olomouc, compliant persons with diabetes, as well as to Insurance Companies and pharma industry in the Czech Republic.

Those who found this chapter worthy of reading surely appreciate the support provided by Palacky University, Teaching Hospital Olomouc, Institute of Specialized Treatments Paseka and other important institutions.
